This proposal outlines a four project program designed to meet the requirements for an Asthma, Allergy and Immunologic Diseases Cooperative Research Center (AAIDCRC). The basic science component of this proposal brings together three internationally recognized scientists, Jean-Pierre Kinet, M.D, Stephen J. GalIi M.D., and Peter F. Weller M.D., with established records of individual and collaborative productivity, each of whom will direct a project investigating high affinity IgE receptor-dependent processes which are relevant to the pathogenesis of asthma. The three projects: project 1-IgE Regulation of Fc epsilon RI: Modulation and Significance; project 2-Anti-FcepsilonRI alpha Autoantibodies in Asthma; and project 3- Airway Eosinophils As Antigen-Presenting Cells in Asthma, are united by a central theme: evaluating the possibility that the high affinity IgE receptor (FcepsilonRI) represents a hitherto unsuspected link between the pathogenesis of "allergic" and "non-allergic" forms of asthma, and that this receptor, in addition to triggering the release of-mediators and cytokines from FcepsilonRI+ effector cells, may also mediate other functions which contribute to the initiation and perpetuation of asthmatic responses. In addition, each project will utilize a common novel murine model, "FcepsilonRI-humanized" mice (described herein) for many of its studies. The synergistic aspects of these projects are a strong rationale for their being funded through an AAIDCRC, which will enhance the opportunities for creative interactions among the participating investigators. In addition to the basic scientific components, this proposal includes a Demonstration and Education Project which will directed by an internationally known researcher in the areas of child health policy and adjustment to childhood chronic illness, James M. Perrin, M.D. This project will examine the impact on measures of asthma morbidity (hospitalization, emergency room and physician/nurse visits, and school participation) of a culturally-sensitive, age-appropriate, cooperative asthma management educational program for children with asthma and their parents. The study, which will be conducted in a high-risk urban community (Chelsea, MA), will, in all phases, examine several child and illness-specific, family, health systems, and environmental variables and will assess the extent to which they predict morbidity from asthma. It will also assess several variations in the site and type of education, and in clinical and demographic characteristics of children and households, and determine whether they affect the benefit of the educational interventions.